Mitogen-activated protein kinase kinase kinase 3

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Q61084 (M3K3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 116. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 3
EC=2.7.11.25

Alternative name(s):
MAPK/ERK kinase kinase 3
Short name=MEK kinase 3
Short name=MEKK 3

Gene names

Name:	Map3k3
Synonyms:	Mekk3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	626 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. Ref.1
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by phosphorylation on Thr-530 By similarity.
Subunit structure	Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2. Interacts with MAP2K5 and SPAG9. Ref.3 Ref.4
Post-translational modification	Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its activity By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 OPR domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: GOC activation of MAPKK activity Inferred from electronic annotation. Source: GOC positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from sequence orthology PubMed 15001576. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from sequence orthology PubMed 15001576. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Map2k5	Q9WVS7	15	EBI-446250,EBI-446144
Traf6	P70196	4	EBI-446250,EBI-448028

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 626

626

Mitogen-activated protein kinase kinase kinase 3

PRO_0000086246

Regions

Domain

44 – 123

OPR

Domain

362 – 622

261

Protein kinase

Nucleotide binding

368 – 376

ATP By similarity

Sites

Active site

489

Proton acceptor By similarity

Binding site

391

ATP By similarity

Amino acid modifications

Modified residue

166

Phosphoserine; by SGK1 Ref.6

Modified residue

250

Phosphoserine By similarity

Modified residue

337

Phosphoserine; by SGK1 Ref.5

Modified residue

340

Phosphoserine Ref.5

Sequences

Sequence

Length

Mass (Da)

Tools

Q61084 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 00EF2442C9E56E0B
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FASTA

626

70,776

        10         20         30         40         50         60 
MDEQEALDSI MKDLVALQMS RRTRLSGYET MKNKDTGHPN RQSDVRIKFE HNGERRIIAF 

        70         80         90        100        110        120 
SRPVRYEDVE HKVTTVFGQP LDLHYMNNEL SILLKNQDDL DKAIDILDRS SSMKSLRILL 

       130        140        150        160        170        180 
LSQDRNHTSS SPHSGVSRQV RIKPSQSAGD INTIYQAPEP RSRHLSVSSQ NPGRSSPPPG 

       190        200        210        220        230        240 
YVPERQQHIA RQGSYTSINS EGEFIPETSE QCMLDPLSSA ENSLSGSCQS LDRSADSPSF 

       250        260        270        280        290        300 
RKSQMSRARS FPDNRKECSD RETQLYDKGV KGGTYPRRYH VSVHHKDYND GRRTFPRIRR 

       310        320        330        340        350        360 
HQGNLFTLVP SSRSLSTNGE NMGVAVQYLD PRGRLRSADS ENALTVQERN VPTKSPSAPI 

       370        380        390        400        410        420 
NWRRGKLLGQ GAFGRVYLCY DVDTGRELAS KQVQFDPDSP ETSKEVSALE CEIQLLKNLQ 

       430        440        450        460        470        480 
HERIVQYYGC LRDRAEKILT IFMEYMPGGS VKDQLKAYGA LTESVTRKYT RQILEGMSYL 

       490        500        510        520        530        540 
HSNMIVHRDI KGANILRDSA GNVKLGDFGA SKRLQTICMS GTGIRSVTGT PYWMSPEVIS 

       550        560        570        580        590        600 
GEGYGRKADV WSLGCTVVEM LTEKPPWAEY EAMAAIFKIA TQPTNPQLPS HISEHGRDFL 

       610        620 
RRIFVEARQR PSAEELLTHH FAQLVY

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase." Blank J.L., Gerwins P., Elliott E.M., Sather S., Johnson G.L. J. Biol. Chem. 271:5361-5368(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Brain.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary gland.
[3]	"JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors." Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P. Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPAG9.
[4]	"Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock." Uhlik M.T., Abell A.N., Johnson N.L., Sun W., Cuevas B.D., Lobel-Rice K.E., Horne E.A., Dell'Acqua M.L., Johnson G.L. Nat. Cell Biol. 5:1104-1110(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP2K3; RAC1 AND CCM2.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND SER-340, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, MASS SPECTROMETRY. Tissue: Melanoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43187 mRNA. Translation: AAB03535.1. BC023781 mRNA. Translation: AAH23781.1.
IPI	IPI00117089.
RefSeq	NP_036077.1. NM_011947.3.
UniGene	Mm.27041.
3D structure databases
ProteinModelPortal	Q61084.
SMR	Q61084. Positions 42-126, 336-624.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q61084. 3 interactions.
MINT	MINT-1531397.
PTM databases
PhosphoSite	Q61084.
Proteomic databases
PaxDb	Q61084.
PRIDE	Q61084.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002044; ENSMUSP00000002044; ENSMUSG00000020700.
GeneID	26406.
KEGG	mmu:26406.
Organism-specific databases
CTD	4215.
MGI	MGI:1346874. Map3k3.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104370.
HOGENOM	HOG000049130.
HOVERGEN	HBG006303.
InParanoid	Q61084.
KO	K04421.
OMA	QALHSIM.
OrthoDB	EOG4WQ122.
Enzyme and pathway databases
BRENDA	2.7.12.2. 3474.
Gene expression databases
ArrayExpress	Q61084.
Bgee	Q61084.
CleanEx	MM_MAP3K3.
Genevestigator	Q61084.
GermOnline	ENSMUSG00000020700. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000270. OPR_PB1. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. [Graphical view]
Pfam	PF00564. PB1. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00666. PB1. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MAP3K3. mouse.
NextBio	304381.
SOURCE	Search...

Entry information

Entry name

M3K3_MOUSE

Accession

Primary (citable) accession number: Q61084

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents